Impact of comorbidities on oncological outcomes of Japanese patients with high grade soft tissue sarcomas.

BACKGROUND: Considering the invasiveness of standard multidisciplinary approaches used for the treatment of soft tissue sarcoma, including surgery with wide margins, intensive chemotherapy, and radiotherapy, evaluation of comorbidities in high-grade soft tissue sarcoma patients is essential. Several previous studies have reported the impact of comorbidities on the survival of soft tissue sarcoma patients. Patient health status differs between nationalities or ethnic groups and only limited data has been reported with respect to the impact of comorbidities on Japanese soft tissue sarcoma patients. METHODS: The incidence of each comorbidity, relationship between comorbidities and underlying clinicopathological factors, relationship between treatment status and comorbidities, and impact of comorbidities on disease-specific death in 136 patients with high-grade soft tissue sarcoma at the authors' institution were analyzed. For the evaluation of comorbidities, the updated Charlson comorbidity index was applied. RESULTS: Of the patients, 25% presented with more than one comorbidity. Elderly patients showed a significantly higher incidence of comorbidities (p < 0.0001). Patients with congestive heart failure (p = 0.004), dementia (p < 0.0001), hemiplegia/paraplegia (p < 0.0001), and renal disease (p < 0.0001) showed worse prognosis. Tumor grade (p = 0.01) and updated Charlson comorbidity index (p < 0.0001) were independent risk factors for disease-specific death. CONCLUSIONS: Comorbidity status was a significant risk factor for disease-specific death in Japanese patients with high-grade soft tissue sarcoma. Innovations in comorbidity management may be a means for the improvement of oncological outcomes in soft tissue sarcoma. Given the difficulties in conducting standard randomized control studies in this field, data accumulation from real-world cases appears to be the most practical approach in establishing and applying strategies for the treatment of patients with comorbidities or elderly patients.

Clinical significance of the tail-like pattern in soft-tissue sarcomas on magnetic resonance imaging.

BACKGROUND: An infiltrating abnormal signal around soft-tissue tumors along the fascial, neurovascular, or musculature plane on magnetic resonance imaging (T2-weighted, gadolinium-enhanced T1-weighted, or short-tau inversion recovery) is recognized as the "tail-like pattern". The tail-like pattern was intensively analyzed in myxofibrosarcoma, but not in other sarcomas. We aimed to answer some key questions about the tail-like pattern such as its incidence and effect on oncological outcomes. METHODS: The presence of the tail-like pattern in 114 soft-tissue sarcomas was evaluated on T2-weighted images or gadolinium-enhanced T1-weighted images, or both. We analyzed the incidence of the tail-like pattern in all cases and in specific histological subtypes. We also assessed the clinical backgrounds of the presence of the tail-like pattern and its impact on achieving adequate surgical margins and oncological outcomes, including local recurrence and overall survival. RESULTS: The tail-like pattern was detected in 50% of cases. The tail-like pattern was most common in myxofibrosarcoma and undifferentiated pleomorphic sarcoma, and less common in low-grade sarcomas. Trans-compartmental invasion of the tumor and high-grade malignancy were common clinical backgrounds for the presence of the tail-like pattern. The presence of the tail-like pattern significantly inhibits the achievement of preoperatively planned surgical margins despite planning the margins outside the tail-like pattern area. The tail-like pattern was an independent risk factor for local recurrence. The pattern was not an independent risk factor for worse overall survival, although it was a risk factor in univariate analysis. CONCLUSION: The tail-like pattern is clinically significant in myxofibrosarcomas and other sarcomas with respect to the preoperative evaluation of malignancy by magnetic resonance imaging, and negatively affects successful resection and oncological outcomes. A more sophisticated modality for the evaluation and clinical management of the tail-like pattern is needed in the future.

Preoperative evaluation of intraoperative blood loss during malignant soft tissue tumor resection by ultrasonography.

BACKGROUND: Preoperative evaluation of the risk of surgery-related blood loss in malignant soft tissue tumor resection is difficult because of wide variations in histological subtype, malignancy, location, and size. Ultrasonography is useful for the evaluation of blood flow around a soft tissue tumor and has the potential to preoperatively estimate intraoperative blood loss in tumor resection. To date, there has been no report regarding blood loss evaluation using ultrasonography in this field. PATIENTS AND METHODS: The usefulness of information obtained by ultrasonography, including tumor size, vessel density in the tumor, and blood flow volume in the vessels, was analyzed for the prediction of intraoperative blood loss in malignant soft tissue tumor resection. RESULTS: Vessel density in the tumor and blood flow in the vessels were identified as independent risk factors for blood loss. Using these factors, a new index for the prediction of blood loss was established. Receiver operating characteristic analyses revealed a high area under the curve value (0.80), confirming the accuracy of the index for the prediction of blood loss. CONCLUSION: Ultrasonography is a useful modality for predicting intraoperative blood loss in malignant soft tissue tumor surgery.

Mean Platelet Volume Is Associated with Early Neurological Deterioration in Patients with Branch Atheromatous Disease: Involvement of Platelet Activation.

BACKGROUND: The most attentive clinical problem in patients with branch atheromatous disease (BAD) is early neurological deterioration (END). Although the platelet activation (PA) is involved in pathogenesis, the relationship between PA and END has remained unclear. We investigated clinical data including mean platelet volume (MPV, fL) as a marker for PA to identify clinically useful biomarkers for END. METHODS: A total of 64 patients with BAD were investigated retrospectively, and divided into 2 groups based on whether neurologic symptoms deteriorated or not: BAD with and without END (END and non-END). The END was defined as patients with point increase of 1 or greater in the National Institutes of Health Stroke Scale (NIHSS); non-END was defined as those without such increase. Clinical features such as NIHSS, modified Rankin scale (mRS), laboratory data including MPV, lesion size (LS, mm) on admission, and treatments were compared between the 2 groups. RESULTS: Of 64 patients, 17 cases had an END. The median values of NIHSS, mRS, MPV, and LS on admission were significantly greater in END than in non-END (P < .05, respectively). There was no correlation of MPV with NIHSS, mRS and LS, respectively. The median values of MPV were significantly higher in END than in non-END and control (P < .05, respectively). A receiver operating characteristic curve indicated a value of 10.1 as cutoff level for MPV to discriminate between END and non-END. CONCLUSIONS: High MPV values on admission may be an independent biomarker for END. Physicians should pay more careful attention to END in BAD showing MPV values higher than 10.1 on admission.

Unplanned resection of a soft tissue sarcoma: clinical characteristics and impact on oncological and functional outcomes.

BACKGROUND: Over the past three decades, several studies have reported worse outcomes with unplanned resection for malignant soft tissue tumors. However, the impact of these studies on preventing unnecessary unplanned resection remains unknown. METHODS: In a retrospective survey on the treatment of soft tissue sarcomas, we compared cases of unplanned resection with cases of planned resection in terms of the properties of unplanned resection and the oncological and functional outcomes. For the unplanned resection cases, an additional wide resection was performed. RESULTS: Of 92 cases, unplanned resection was performed in 24 (26 %). Small or subcutaneous tumors were significantly more frequently subjected to unplanned resection. In 17 of 24 unplanned resection cases, residual tumors (70.8 %) were noted. Plastic surgery was more frequently needed for unplanned resection cases. There was no significant difference between the unplanned resection and control cases with regard to oncological outcome. However, as to local recurrence and overall survival, the events occurred only in the cases with residual tumors in the additional wide resection specimen in the unplanned resection group. There was no significant difference in functional evaluation, except for emotional acceptance, which had a better score in the unplanned resection group. CONCLUSIONS: Despite repeated cautions regarding unplanned resection in terms of its inadequate procedure which contradicts the principles of soft tissue sarcoma treatment, unplanned resections are still frequently performed. Perhaps the small size and subcutaneous location of the sarcomas in the unplanned resection group did not evoke the probability of malignancy for the surgeons who initially managed them. Even though an additional wide resection was performed, a residual tumor would lead to a worse outcome. An effective awareness program to avoid unnecessary unplanned resections for soft tissue sarcoma should be considered.

[Cross-reactivity of Instant-View M-1 for detection of benzodiazepine-related drugs and their metabolites in urine].

Immunoassays are useful methods for the determination of regulated drugs in clinical and forensic laboratories. Although the Instant-View M-1 (IV M-1) immunoassay kit is frequently used to screen drugs in laboratories in Japan, basic information about the IV M-1 such as its specificity and reactivity is not available. In this study, we determined the specificity and cross-reactivity of IV M-1 for the detection of benzodiazepine-related drugs and their metabolites in urine. The IV M-1 could detect triazolobenzodiazepines such as triazolam in urine at concentrations > or = 300 ng/mL. However, thienodiazepines such as etizolam could not be detected because of lack of cross reactivity. A correlation was observed between the structure of the metabolites and the reactivity of the kit; 4-hydroxy metabolites of alprazolam and triazolam were detectable, whereas a-hydroxy metabolites were not. Furthermore, 7-amino metabolites such as nitrazepam could not be detected at any concentration, including high concentrations. The specificity and reactivity of various kits used for detection of drugs in urine are different. Therefore, it is necessary to consider the basic features of the kit used while assessing the results obtained.

Pearls & Oy-sters: Cognitive and Affective Dysfunction Caused by a Small Cerebellar Hemangioblastoma.

The primary function of the cerebellum is the coordination and regulation of movement; therefore, cerebellar tumors usually present with ataxia, dysarthria, and vertigo. Large tumors also cause elevated intracranial pressure that may lead to a disturbance of consciousness. Furthermore, it has become increasingly evident that the cerebellum plays a substantial role in cognitive and affective processing. A 44-year-old female patient presented with a 1-month history of depression and flat affect. She had no cerebellar symptoms including no coordination dysfunction or dysarthria. Cognitive function tests revealed impairments in attention, execution, and processing speed. Hamilton Depression Scale and Hospital Anxiety Depression Scale indicated moderate-to-severe depression. Magnetic resonance (MR) imaging revealed a 7-mm enhancing lesion in the culmen of the cerebellar vermis with surrounding edema. Technetium-99m ethyl cysteinate dimer single-photon emission tomography (SPECT) showed hypoperfusion in the left frontal lobe. Although she was initially treated with corticosteroids for presumed sero-negative autoimmune encephalitis, her symptoms persisted. She then underwent cerebellar lesion resection. The histologic diagnosis was hemangioblastoma. The patient's symptoms dramatically improved within 1 week of resection, including improved batteries for cognitive function and depression. Complete regression of cerebellar edema and left frontal lobe hypoperfusion was observed on MR and SPECT images, respectively. This case reiterates the crucial influence of the cerebellum on cognitive and affective function. Moreover, cognitive dysfunction may be masked in cases with focal cerebellar symptoms or elevated intracranial pressure and, consequently, not adequately evaluated.

Surgical site infection in malignant soft tissue tumors.

BACKGROUND: Postoperative wound complications, including surgical site infections, which frequently occur in the course of management of musculoskeletal sarcomas, sometimes necessitate repeat surgeries, including amputation, and may result in a prolonged healing time, prolonged hospital stay, or fatal outcome. A comprehensive understanding of surgical site infections associated with specific diseases is needed to reduce the risk. METHODS: This series comprised 84 patients with malignant soft tissue tumors treated at our institute. The occurrence rate, management modality and clinical course of surgical site infections, impact of surgical site infections on the length of hospitalization, risk factors for the development of surgical site infections, and the impact of surgical site infections on the oncological outcomes were analyzed. Surgical site infection was defined according to Centers for Disease Control and Prevention guidelines. RESULTS: Surgical site infections occurred in 7 cases (8.3%). Although successful clinical cure was achieved in all cases, surgical site infection was identified as one of the independent risk factors for prolongation of hospitalization. Both univariate and multivariate analyses identified larger intraoperative blood loss and a trunk location as risk factors associated with deep infections. No association was detected between age, tumor grade, chemotherapy, tumor volume, or plastic surgery and the risk of surgical site infections. Although the differences were not statistically significant, patients with surgical site infections showed worse oncological outcomes in terms of local recurrence and total survival. CONCLUSION: The incidence rate of surgical site infection was larger than that associated with conventional orthopedic surgeries, such as osteosynthesis, spine surgery, or arthroplasty. Surgical site infections remain a critical and frequent complication of surgical treatment of soft-tissue malignancies and often result in prolongation of hospital stay. Although practical options to prevent surgical site infections seem quite limited, the present data provide a rationale for perioperative evaluation in patients at a high risk of surgical site infections.

D-dimer levels as a prognostic factor for determining oncological outcomes in musculoskeletal sarcoma.

BACKGROUND: Plasma d-dimer levels have been associated with the status of tumor progression or oncological outcomes in cancer. Although there are many evidences suggesting the involvement of procoagulant trend in musculoskeletal sarcoma, no clinical data on d-dimer levels and oncological outcome of musculoskeletal sarcoma has been reported. METHODS: In this study, we included a total of 85 patients who were diagnosed with musculoskeletal sarcoma and treated at our institute. Plasma d-dimer levels were determined before performing any clinical intervention, including open biopsy, chemotherapy, radiotherapy or tumor resection. We evaluated the effect of d-dimer levels and other clinicopathological factors on oncological outcomes of patients. RESULTS: Upregulation of plasma d-dimer levels proved to be an independent risk factor for metastasis and lethal outcome of patients with musculoskeletal sarcoma. CONCLUSIONS: Upregulation of plasma d-dimer levels were indicated poor oncological outcome in metastasis and total survival rate of musculoskeletal sarcoma patients. Hence d-dimer levels may be a helpful marker for evaluating the tumor progression status and prognosis of musculoskeletal sarcoma.

Treatment outcome of enchondroma by simple curettage without augmentation.

BACKGROUND: Simple curettage for enchondroma without augmentation, known to lead to spontaneous bone consolidation at the curettage site, is a potential standard treatment for this condition. However, few detailed data comparing the results of this technique with conventional methods including reconstruction are available, and the relation between the postoperative completion period for bone consolidation and preoperative independent variables is not known. METHODS: The subjects included 38 patients with enchondroma treated with simple curettage without augmentation. A historical group of patients with enchondroma treated with hydroxyapatite reconstruction was enrolled as controls. Treatment outcomes, including perioperative complications (e.g., infection, functional loss, recurrence, postoperative fracture), were surveyed. Differences in the period needed for bone formation among the patient groups defined by various preoperative patient conditions were also analyzed. RESULTS: The follow-up period ranged from 12 to 60 months (average 24.3 months). During the follow-up period, no surgery-related complications occurred. Bone formation was confirmed in all cases 3-20 weeks (average 6.5 weeks) postoperatively. Tumor size represented by two-dimensional measurements was significantly correlated with the bone formation period. Polycystic lesions required a prolonged postoperative bone formation period compared with monocystic lesions. The bone formation period did not significantly differ between the simple curettage group and the historical control group. CONCLUSIONS: Simple curettage without augmentation proved to be a safe, promising modality for the treatment of small enchondromas in the hand and foot.

Short-term postoperative mortality events in patients over 80 years of age with hip fracture: analysis at a single institution with limited medical resources.

BACKGROUND: Lethal events represent the most important complication in the treatment of hip fracture in elderly patients. Despite the increasing chance for treatment of such conditions, few data regarding risk factors associated with lethal events have been determined for ordinary hospitals with limited medical and human resources, particularly in Japan. METHODS: The incidence of postoperative lethal events and related preoperative risk factors in extremely elderly patients (>80 years) with hip fracture were retrospectively analyzed in our hospital for the past 2 years. RESULTS: Lethal events occurred in 11 (10.7%) of 103 patients within 3 months postoperatively. In both univariate and multivariate analyses, an elevated number of co-morbidities and preoperative respiratory dysfunction were identified as significant risk factors. Delay in surgery was not a risk factor for lethal events. CONCLUSIONS: A valid reason for delay is the need to stabilize concurrent medical conditions due to multiple co-morbidities in extremely elderly patients with hip fracture. Considering the limited resources and extreme age of the subjects, the mortality rate in the present study was quite acceptable. Patients, families of patients, and physicians should recognize the increased risk of mortality for patients with significant risk factors in the surgical treatment of hip fracture.

Venous thromboembolism in the management of patients with musculoskeletal tumor.

BACKGROUND: Although patients with musculoskeletal tumors are at risk of venous thromboembolism (VTE), few detailed studies on the incidence, clinical course, and risk factors of this condition have been reported. METHODS: A total of 299 patients with musculoskeletal tumors during the preceding 3 years were enrolled. D-dimer (DD) levels on admission and on postoperative days 1, 7, and 14 were routinely assessed. For patients who were receiving chemotherapy, an examination was performed every 2-3 days for the survey. Multidetector-row computed tomography (MDCT) was used for the detection of VTE in patients with DD levels > 10 µg/ml. The incidence of clinically detected VTE and the clinical courses of the patients with VTE were reviewed. The risk factors for VTE were analyzed. For statistical analysis, Fisher's exact test, the Mann-Whitney U-test, and logistic regression were used. RESULTS: VTE was detected in eight cases (2.7%). Six cases were detected postoperatively, and the remaining two cases were detected during chemotherapy. Pulmonary embolism was evident in four cases. No VTE-related lethal events were detected during the study period. In the univariate analysis, malignancy (P = 0.003), chemotherapy (P = 0.004), plastic surgery (P = 0.006), tumor size (P = 0.008), and elevated DD levels at admission (P = 0.03) were found to be significant risk factors for VTE. Among these factors, the multivariate analysis indicated that tumor size (P = 0.00 006), plastic surgery (P 0. 01), and chemotherapy (P = 0.02) were independent risk factors. CONCLUSIONS: The incidence and risk factors for VTE in the management of musculoskeletal tumor patients by screening DD levels combined with MDCT were analyzed. For patients at risk, prospective surveys for VTE should be considered in the future.

Association of Dermatomyositis Sine Dermatitis With Anti-Nuclear Matrix Protein 2 Autoantibodies.

Importance: Reports on dermatomyositis (DM) sine dermatitis (DMSD) are scarce, and the concept of the disease has not been widely accepted. Objective: To confirm the existence of DMSD, determine its prevalence, and characterize its serologic features. Design, Setting, and Participants: This is a cohort study that reviewed clinical information, laboratory data, and muscle pathology slides from January 2009 to August 2019. We further assessed the follow-up data of 14 patients with DMSD. The median (interquartile range) follow-up period was 34 (16-64) months. Muscle biopsy samples, along with clinical information and laboratory data, were sent to a referral center for muscle diseases in Japan for diagnosis. Of patients whose myopathologic diagnosis was made at the National Center of Neurology and Psychiatry between January 2009 and August 2019, 199 patients were eligible for inclusion. These patients underwent full investigation for DM-specific autoantibodies (against transcriptional intermediary factor γ, Mi-2, melanoma differentiation-associated gene 5, nuclear matrix protein 2 [NXP-2], and small ubiquitin-like modifier activating enzyme ); however, 17 patients were excluded because their muscle fibers did not express myxovirus resistance protein A, a sensitive and specific marker of DM muscle pathology. Main Outcomes and Measures: Diagnosis of DMSD was based on the absence of a skin rash at the time of muscle biopsy. Results: Of the 182 patients, 93 were women (51%) and 46 were children (25%) (<18 years). Fourteen patients (8%) had DMSD and none were clinically diagnosed with DM. Among the 14 patients with DMSD, 12 (86%) were positive for anti-NXP-2 autoantibodies, while the remaining 2 were positive for anti-transcriptional intermediary factor γ and anti-Mi-2 autoantibodies, respectively. Only 28% of patients (47 of 168) with a skin rash were positive for anti-NXP-2 autoantibodies, indicating a significant association between anti-NXP-2 autoantibodies and DMSD (86% [12 of 14] vs 28% [47 of 168]; P < .001). This association was also supported by multivariable models adjusted for disease duration (odds ratio, 126.47; 95% CI, 11.42-1400.64; P < .001). Conclusions and Relevance: Dermatomyositis sine dermatitis does exist and accounts for 8% of patients with DM confirmed with muscle biopsy. Dermatomyositis sine dermatitis is significantly associated with anti-NXP-2 autoantibodies, which contrasts with anti-MDA5 DM, which is typically clinically amyopathic in presentation. It is essential to distinguish DMSD from other types of myositis because DM-specific therapies that are currently under development, including Janus kinase inhibitors, may be effective for DMSD.

Calreticulin as A Novel Potential Metastasis-Associated Protein in Myxoid Liposarcoma, as Revealed by Two-Dimensional Difference Gel Electrophoresis.

Myxoid liposarcoma (MLS) is a mesenchymal malignancy. To identify innovate seeds for clinical applications, we examined the proteomes of primary tumor tissues from 10 patients with MLS with different statuses of postoperative metastasis. The protein expression profiles of tumor tissues were created, and proteins with differential expression associated with postoperative metastasis were identified by two-dimensional difference gel electrophoresis (2D-DIGE) and mass spectrometry. The validation was performed using specific antibodies and in vitro analyses. Using 2D-DIGE, we observed 1726 protein species and identified proteins with unique expression levels in metastatic MLS. We focused on the overexpression of calreticulin in metastatic MLS. The higher expression of calreticulin was confirmed by Western blotting, and gene silencing assays demonstrated that reduced expression of calreticulin inhibited cell growth and invasion. Our findings suggested the important roles of calreticulin in MLS metastasis and supported its potential utility as a prognostic biomarker in MLS. Further investigations of the functional properties of calreticulin and other proteins identified in this study will improve our understanding of the biology of MLS and facilitate novel clinical applications.

Observation of quadrature squeezing in a chi2 nonlinear waveguide using a temporally shaped local oscillator pulse.

We report on the generation of quadrature squeezed light at 1.535 microm via single-pass optical parametric amplification in a periodically poled MgO:LiNbO(3) waveguide, and detection with a temporally shaped local oscillator. Squeezing of -4.1 dB was directly measured using the shaped local oscillator. Classical parametric gain of the shaped pulse was also investigated; a deamplification gain of -12.1 dB was observed with the amplification gain of only +13.8 dB. We experimentally show that the use of shaped pulse as local oscillator in homodyne detection allows us efficient squeezing detection with near-unit mode-matching efficiency.

Preoperative Ultrasonographic Evaluation for Malignancy of Soft-Tissue Sarcoma: A Retrospective Study.

BACKGROUND: Ultrasonography is useful for distinguishing between benign and malignant soft-tissue tumors. However, no study has focused on its usefulness in the differential diagnosis between low-grade and high-grade soft-tissue sarcomas. We conducted a retrospective study to determine the usefulness of the parameters of ultrasonograph and to develop a practical scoring system for distinguishing between high-grade and low-grade sarcomas. METHODS: Twenty-two cases of low-grade and 43 cases of high-grade malignant soft-tissue sarcoma were enrolled. Ultrasonography parameters including the longest diameter, depth of the tumor, echogenicity, tumor margin, and vascularity defined according to Giovagnorio's criteria were analyzed as factors to distinguish between the two types of sarcoma. Significant factors were entered into a multivariate model to define the scores for distinction according to the odds ratio. The usefulness of the score was analyzed via receiver operating characteristic analyses. RESULTS: In univariate analysis, tumor margin, echogenicity, and vascularity were significantly different between low- and high-grade sarcomas. In the multivariate regression model, the odds ratio for high-grade vs. low-grade sarcoma was 8.8 for tumor margin, 69 for echogenicity, and 8.3 for vascularity. Scores for the risk factors were defined as follows: 1, ill-defined margin; 2, hypoechoic echogenicity; and 1, type IV in Giovagnorio's criteria. The sum of each score was confirmed by receiver operating characteristic analysis. The area under the curve was 0.95, with a cut-off score of 3, indicating that the scoring system was useful. CONCLUSION: The ultrasonography parameters of tumor margin, echogenicity, and vascularity are useful for distinguishing between low- and high-grade sarcomas.

Differential diagnosis between benign and malignant soft tissue tumors utilizing ultrasound parameters.

PURPOSE: Preoperative discrimination between benign and malignant soft tissue tumors is critical for the prevention of excess application of magnetic resonance imaging and biopsy as well as unplanned resection. Although ultrasound, including power Doppler imaging, is an easy, noninvasive, and cost-effective modality for screening soft tissue tumors, few studies have investigated reliable discrimination between benign and malignant soft tissue tumors. METHODS: To establish a modality for discrimination between benign and malignant soft tissue tumors using ultrasound, we extracted the significant risk factors for malignancy based on ultrasound information from 40 malignant and 56 benign pathologically diagnosed soft tissue tumors and established a scoring system based on these risk factors. RESULTS: The maximum size, tumor margin, and vascularity evaluated using ultrasound were extracted as significant risk factors. Using the odds ratio from a multivariate regression model, a scoring system was established. Receiver operating characteristic analyses revealed a high area under the curve value (0.85), confirming the accuracy of the scoring system. CONCLUSION: Ultrasound is a useful modality for establishing the differential diagnosis between benign and malignant soft tissue tumors.

Vertebral Artery Stump Syndrome.

Carotid stump syndrome is a well-documented embolic source for ischemic stroke. However, few cases have been reported of a similar condition - termed vertebral artery stump syndrome - which affects the posterior circulation after vertebral artery origin occlusion. We herein report a case of infarction of the right superior cerebellar artery and left posterior inferior cerebellar artery territories due to vertebral artery stump syndrome. In this interesting case, a turbulent flow at the distal side of the vertebral artery occlusion was captured on ultrasonography, and was identified as the probable mechanism of vertebral artery stump syndrome.

Development of Stemness in Cancer Cell Lines Resistant to the Anticancer Effects of Zoledronic Acid.

BACKGROUND: Drug resistance is closely related to cancer cell stemness, that is acquired along with resistance to various anticancer agents. However, this has not been investigated as a potential mechanism underlying cancer cell resistance to zoledronate, that is used to suppress bone metastasis. MATERIALS AND METHODS: Zoledronate-resistant A549 lung cancer and MG63 osteosarcoma cell lines were established by repeated treatment with sub-lethal concentrations of zoledronate. Expression levels of the stem cell marker NANOG, cMYC, octamer-binding transcription factor 4, and sex-determining region Y-box 2 were evaluated and sphere formation was compared between parental and resistant cell lines. Tumourigenicity was assessed in vivo. RESULTS: Stem cell marker expression was up-regulated and sphere formation was enhanced in resistant compared to parental cells and showed greater tumour formation capacity in mice. CONCLUSION: Repeated treatment of malignant tumour cell lines with zoledronate, induces the development of drug resistance and stemness.